- definitions: virulence and all that
- transmission modes
- tradeoff theory
- beyond the tradeoff theory
17 October 2016
outline
definitions and context
definitions of virulence
- something bad about an infectious disease (media/general public)
- infectivity (plant/molecular biology)
- decrease in host fitness (evolutionary biology)
- rate of disease-induced mortality (links host & parasite fitness)
other properties
- host castration
(host fitness \(\searrow\) without death) - parasite clearance by host (immunity)
(parasite fitness \(\searrow\)) - case mortality
(probability of host death) - immunopathology
(host and parasite fitness \(\searrow\)?)
Q: which of these represent virulence?
other aspects of host-parasite interaction
virulence depends on both host and parasite
- exploitation (parasite)
- pathogenesis (parasite)
- resistance (host)
tolerance (host)
classical theory and its problems
classical theory
Parasites evolve lower virulence over time for the good of the species; don't want to hurt host
Given enough time a state of peaceful coexistence usually becomes established between any host and parasite … throughout nature, infection without disease is the rule rather than the exception (Dubos, 1980)
For nature, survival of the species is all that counts (Macfarlane Burnet & White, 1972)
evolution …
- variation in parasite fitness (between-host replication rate)
- relationship between parasite traits and fitness
- heritability of parasite traits
classical theory: evidence? examples?
- syphilis (Knell, 2004)
virgin-soil epidemics
what other factors might explain virulence of new outbreaks?
counterexamples: malaria, tuberculosis …
problems with classical theory
- group selection
- effect of cheaters: why not drive the host population to extinction?
tradeoff theory
tradeoff theory
- intermediate virulence evolves due to host-level selection
- tradeoff between transmission rate (infections/host/time) and virulence (mortality/time)
- \(R_0\) (total transmission per generation) maximized at intermediate virulence
modes of transmission
Modes of transmission may drive parasite evolution
- environmental (e.g. water)
- vector-borne
- needle-borne
- direct transmission
- vertical transmission
- necrotransmission (e.g. anthrax)
what's your prediction about nosocomial (hospital-borne) transmission?
myxomatosis
- Viral disease; mild in Brazilian rabbits (Sylvilagus brasiliensis); virulent in European rabbits (Oryctolagus cuniculus)
- Vector-borne (by mosquitos and fleas)
- Introduced (several times) in Australia to control introduced rabbits, finally spread 1950-1951.
Wikipedia, Richard Harvey
myxomatosis (cont.)
- Case mortality originally >99%, rabbit pops initially \(\searrow\) 90%
- CM initially dropped to 90%, then further
- Resistance: CM of grade III strain drops from 90% to about 50% as populations experience more epizootics.
- At the same time mean virus grade drops from I to III, then rebounds
myxomatosis virulence over time
(Fenner et al., 1956)
evidence for tradeoff theory:
- Higher grades (higher case mortality) also have faster mortality (<13 days to >50 day survival as CM goes from >99% to <50%).
- Skin virus titer is also higher (and increases faster with time) for higher grades.
- Mosquito infection probability is proportional to skin titer
Bottom line: myxomavirus probably still reduces populations somewhat, but the Australians are looking for other biocontrol solutions (calicivirus).
tradeoff theory
Maximizing \(R_0\):
the tradeoff theory and beyond
- tradeoff theory seems useful in many cases (Alizon et al., 2009)
- but … critics (Ebert & Bull, 2003)
- within-host competition will generally increase virulence
- (when is this likely to be important?)
- coincidental virulence: spillover epidemics
- short-sighted evolution: e.g. meningitis (Levin & Bull, 1994)
- spatial structure (Boots & Mealor, 2007)
- transient virulence (Bolker et al., 2010)
- the devil is often in the details
testing theories
- real-world experiments are hard! (ethics, logistics, time …)
- laboratory evolution (Berngruber et al., 2013)
- build models
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HIV virulence evolution
HIV within-host 'life history'
evolution of HIV virulence
(Shirreff et al., 2011)
HIV virulence: model sensitivity
References
Alizon, S., Hurford, A., Mideo, N., & Baalen, M. van. (2009). Virulence evolution and the trade-off hypothesis: History, current state of affairs and the future. J. Evol. Biol., 22, 245–259. http://doi.org/10.1111/j.1420-9101.2008.01658.x
Berngruber, T. W., Froissart, R., Choisy, M., & Gandon, S. (2013). Evolution of virulence in emerging epidemics. PLoS Pathog, 9(3), e1003209. http://doi.org/10.1371/journal.ppat.1003209
Bolker, B. M., Nanda, A., & Shah, D. (2010). Transient virulence of emerging pathogens. J. R. Soc. Interface, 7(46), 811–822.
Boots, M., & Mealor, M. (2007). Local interactions select for lower pathogen infectivity. Science, 315(5816), 1284–1286.
Dubos, R. J. (1980). Man Adapting. Yale University Press.
Ebert, D., & Bull, J. J. (2003). Challenging the trade-off model for the evolution of virulence: Is virulence management feasible? Trends Microbiol, 11(1), 15–20.
Fenner, F., Day, M. F., & Woodroofe, G. M. (1956). Epidemiological consequences of the mechanical transmission of myxomatosis by mosquitoes. J Hyg (London), 54(2), 284–302.
Knell, R. J. (2004). Syphilis in Renaissance Europe: Rapid evolution of an introduced sexually transmitted disease? Proc R Soc London B, 271, S174–S176.
Levin, B. R., & Bull, J. J. (1994). Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol, 2, 76–81.
Macfarlane Burnet, F., & White, D. O. (1972). Natural History of Infectious Disease. CUP Archive.
Shirreff, G., Pellis, L., Laeyendecker, O., & Fraser, C. (2011). Transmission selects for HIV-1 strains of intermediate virulence: A modelling approach. PLoS Computational Biology, 7(10), e1002185. http://doi.org/10.1371/journal.pcbi.1002185